Platelet-monocyte interaction amplifies thromboinflammation through tissue factor signaling in COVID-19.
Eugenio D HottzRemy Martins-GonçalvesLohanna PalhinhaIsaclaudia G Azevedo-QuintanilhaMariana M CamposCarolina de Queiroz SacramentoJairo Ramos TemerozoVinicius Cardoso SoaresSuelen Silva Gomes DiasLívia TeixeiraÍcaro Maia Santos de CastroCassia RighyThiago Moreno L SouzaPedro KurtzBruno Bezerril AndradeHelder I NakayaRobson Q MonteiroFernando Luiz Cyrino OliveiraPatrícia Torres BozzaPublished in: Blood advances (2022)
Accumulating evidence into the pathogenesis of COVID-19 highlights a hypercoagulability state with high risk of life-threatening thromboembolic complications. However, the mechanisms of hypercoagulability and their link to hyperinflammation remain poorly understood. Here, we investigate functions and mechanisms of platelet activation and platelet-monocyte interactions in inflammatory amplification during SARS-CoV-2 infection. We used a combination of immunophenotyping, single-cell analysis, functional assays, and pharmacological approaches to gain insights on mechanisms. Critically ill patients with COVID-19 exhibited increased platelet-monocyte aggregates formation. We identified a subset of inflammatory monocytes presenting high CD16 and low HLA-DR expression as the subset mainly interacting with platelets during severe COVID-19. Single-cell RNA-sequencing analysis indicated enhanced fibrinogen receptor Mac-1 in monocytes from patients with severe COVID-19. Monocytes from patients with severe COVID-19 displayed increased platelet binding and hyperresponsiveness to P-selectin and fibrinogen with respect to tumor necrosis factor-α and interleukin-1β secretion. Platelets were able to orchestrate monocyte responses driving tissue factor (TF) expression, inflammatory activation, and inflammatory cytokines secretion in SARS-CoV-2 infection. Platelet-monocyte interactions ex vivo and in SARS-CoV-2 infection model in vitro reciprocally activated monocytes and platelets, inducing the heightened secretion of a wide panel of inflammatory mediators. We identified platelet adhesion as a primary signaling mechanism inducing mediator secretion and TF expression, whereas TF signaling played major roles in amplifying inflammation by inducing proinflammatory cytokines, especially tumor necrosis factor-α and interleukin-1β. Our data identify platelet-induced TF expression and activity at the crossroad of coagulation and inflammation in severe COVID-19.
Keyphrases
- coronavirus disease
- sars cov
- dendritic cells
- single cell
- poor prognosis
- peripheral blood
- respiratory syndrome coronavirus
- oxidative stress
- endothelial cells
- binding protein
- early onset
- rheumatoid arthritis
- rna seq
- high throughput
- atrial fibrillation
- machine learning
- escherichia coli
- drug induced
- artificial intelligence
- big data
- case report
- staphylococcus aureus
- electronic health record
- biofilm formation
- data analysis